Tissue engineering involves the synthesis of biologically relevant tissue for a wide range of applications including wound healing and the replacement or support of damaged organs. A common strategy is culturing target specific cells in vitro in a scaffold followed by implantation of the scaffold in a biological organism. As a logical cellular source for tissue engineering, stem cells have attracted a great deal of attention due to their relatively fast proliferation rate and diverse differentiation potential to various phenotypes. These include cells derived from several origins: induced pluripotent stem cells from fibroblasts, mesenchymal stem cells from bone marrow and adult stem cells from adipose tissue. Stem cells distinctively self-renew and their terminal differentiation depends on the influence of soluble molecules (e.g., growth factors, cytokines) as well as physical and biochemical interactions with scaffolds. Cellular behavior and subsequent tissue development at the cell-scaffold interface therefore involve adhesion, motility, proliferation, differentiation and functional maturity. The physicochemical properties of a scaffold, such as bulk chemistry, surface chemistry, topography, three-dimensionality and mechanical properties, all influence cellular response. Bulk chemistry can control cytotoxicity, as most scaffolds are made of biodegradable materials and must eventually release the by-products of their degradation. The effect of surface chemistry is often mediated by instantly adsorbed proteins such as fibronectin, collagen, fibrinogen, vitronectin, and immunoglobulin that affect phenotype, viability, and morphology, as well as proliferation and differentiation.
Studies regarding the effect of surface topography and texture on cellular response have been conducted. Stem cells are known to recognize topographical features of the order of hundreds of nanometers to several micrometers, and exhibit distinctive genomic profiles in the absence of biochemical differentiation cues and a commitment to terminal differentiation. Electrospun scaffolds are ideal matrices for two dimensional or three dimensional culture of the cells providing non-woven nano- to micro-sized fibrous microstructures typically having relative porosities of 70-90%. Natural biodegradable materials such as collagen, gelatin, elastin, chitosan, and hyaluronic acid, as well as synthetic biodegradable polymers such as poly(e-caprolactone) (PCL), poly(glycolic) acid (PGA) and poly(lactic) acid (PLA), have been electrospun for chondral and osseous applications.
In general, the broad utility of electrospun scaffolds for tissue engineering, wound healing, and organ replacement is clear (see Modulation of Embryonic Mesenchymal Progenitor Cell Differentiation via Control Over Pure Mechanical Modulus in Electrospun Nanofibers, Nama et al., Acta Biomaterialia 7, 1516-1524 (2011), which is incorporated by reference herein in its entirety, for all purposes) and the present invention provides polymer fiber constructs for these and other applications. Alignment of fibers produced during electrospinning has previously been achieved by various methods including, for example, high velocity collection of fibers (e.g., on the surface of a high velocity rotating mandrel) and alternating collection of fibers from one grounded electrode to another on an immobile surface or in the air. Current methods of electrospinning aligned fibers are not known to achieve the ideal alignment of fibers observed in the human body, such as, for example, in brain tissue. Therefore, improvements in alignment must be made in order to obtain the high degree of alignment necessary for an in vitro model of human tissue.